Page 128 - Read Online

Page 10 of 19 Kim et al. Soft Sci 2023;3:18 https://dx.doi.org/10.20517/ss.2023.08

Next, we tested HATYR/PEDOT:PSS with different concentrations (0.5%, 1%, 2%, and 3%) of HATYR to
quantitatively and qualitatively characterize injectability. First, the mechanical modulus of each HATYR/
PEDOT:PSS sample was determined. As the concentration of HATYR increased at an oscillation frequency
of 1 Hz, the storage modulus increased from 65, 223, 390, and 480 Pa at HATYR concentrations of 0.5%, 1%,
2%, and 3%, respectively, indicating robust gelation with increasing tyramine and sulfone crosslinking
[43]
[Supplementary Figure 5A] .
Recently, there have been many reports on the use of organic-based conductive hydrogels in various
[82]
bioelectronic applications, including epidermal electrophysiological recording , 3D printable and
cytocompatible conductive bioink , and peripheral nerve interfacing . However, to the best of our
[83]
[84]
knowledge, there has not yet been a reported case of a biocompatible, multi-channel recording electrode
array platform fabricated from purely conductive hydrogel, not to mention a demonstration of MRI
compatibility from a hydrogel ECoG array.

In addition, hydrogels fabricated with commonly used photolithography techniques are incompatible with
complex geometries: photolithography is a multistep process that is increasingly more expensive and
[85]
delicate with finer structures . Moreover, injection- or extrusion-based printing that depends on the
viscoelasticity of the hydrogel has advantages in cytotoxicity and high-fidelity post-printing. Therefore,
viscoelasticity was observed with increasing HATYR concentrations, and all the hydrogel samples were
found to be shear thinning, which is injectable [Supplementary Figure 5B] . However, the optimal
[86]
concentration of HATYR should be determined qualitatively for extruded hydrogel diameters of less than
200 μm for higher-resolution patterning in array designs. A limitation of fabricating conductive hydrogel
electrode arrays through extrusion is the dependence of dimensions on the size of the injection needle.
Commercially available needles vary from 18 to 30 G (inner diameter of 0.838 to 0.159 μm); thus, using
injection to design array design comes at the cost of large width. Therefore, we tested the injectability of
each HATYR/PEDOT:PSS formulation using a 30 G needle, the thinnest inner diameter available to us. The
tyramine moieties allowed for a stronger ionic crosslinking with PSS than with the HA backbone, thereby
increasing the overall viscoelasticity of the formulation and injectable using a 30 G needle. Although 0.5%
HATYR/PEDOT:PSS showed the formation of continuous filaments, 1% HATYR/PEDOT:PSS extruded
with slight fluctuations, 2% HATYR/PEDOT:PSS was injected with granular and brittle textures, and 3%
HATYR/PEDOT:PSS could not be extruded with a 30 G needle [Supplementary Figure 5C]. Therefore, a
HATYR concentration of 0.5% was chosen for all subsequent experiments.

-1
Previous FT-IR spectra analysis showed that C=O stretching at 1,736 cm of the HA backbone, although
weak, also participates in crosslinking. To investigate this mechanically, an equal concentration (0.5%) of
pristine HA was compared to that of HATYR when mixed with the PEDOT:PSS solution. At an oscillation
frequency of 1 Hz, the storage modulus decreased by more than 4-fold from 65 to 14 Pa when tyramine was
absent in the backbone [Figure 2E]. In addition, the viscoelasticity decreased, thereby losing linear
injectability due to absence of tyramine moieties [Figure 2F].

A recurring problem with hydrogel bioelectronics is that hydrogels are intrinsically hydrophilic and can be
easily dissolved when interfaced with wet surfaces. Therefore, ICH was prepared by adding glycerol to
HATYR/PEDOT:PSS hydrogel to improve its resistance to dissolution. Firstly, the addition of glycerol did
not hinder injectability and was found to be printable [Figure 2G]. Feasibility in 3D extrusion printing
demonstrates the scalable and repeatable fabrication process of the electrode array for potential
mechanization and precision healthcare. While molding may also be a consideration, it does not provide
flexibility in design nor in the manufacturing process; thus, 3D printing was demonstrated for feasibility in